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Biomedical subjects

Y Cormier

Publications and source records attributed to Y Cormier.

At least 19 recordsLinked to original sources
PubMed1999

Expression of heat shock protein 72 by alveolar macrophages in hypersensitivity pneumonitis.

The current study was done to look at a possible role of heat shock proteins (HSPs) in hypersensitivity pneumonitis (HP). The specific aims were to determine whether there was a difference in the expression of HSP72 in alveolar macrophages (AMs) between mice challenged with HP antigen and saline-treated control mice and between AMs obtained by bronchoalveolar lavage from 18 patients with HP and 11 normal subjects. The expression of HSP72 was studied under basal conditions and under a mild heat shock. HSP72 expression by AMs in response to in vitro stimulation with Saccharopolyspora rectivirgula was lower in AMs of control mice than in those of HP animals. HSP72 was constitutively expressed in AMs of both normal and HP subjects. Densitometric ratios showed that AMs from normal subjects responded to heat shock with a 39 degrees C-to-37 degrees C ratio of 1.72 +/- 0.18 (mean +/- SE), and AMs from HP patients responded with a ratio of 1.16 +/- 0.16 (P = 0.0377). This decreased induction by additional stress of AMs could lead to an altered immunoregulatory activity and account for the inflammation seen in HP.

Animals↗
PubMed1999

Common respiratory viruses in lower airways of patients with acute hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP), a lung disease with "flulike" symptoms, results from repeated exposures to well defined, nonpathogenic antigens. This study examined whether respiratory viruses are present in the lower airways, the likely site of hypersensitivity reaction, in patients with HP. The polymerase chain reaction (PCR) method was used to test for 10 common respiratory viruses in bronchoalveolar lavage (BAL) cells obtained from patients with acute HP and from unexposed healthy volunteers. Immunocytochemistry was subsequently used to localize viral proteins within BAL cells. The results of PCR showed that influenza A virus was the most frequently detected virus in the BAL cells of our study patients (six of 13) and control subjects (two of six). Influenza A proteins were detected within alveolar macrophages in nine of 13 patients and in two of six control subjects. The number of total BAL cells, but not lymphocytes, was higher in patients with documented influenza A proteins than in patients with no influenza A proteins (p = 0.017) and correlated with the proportion of influenza-A-positive alveolar macrophages (r = 0.7; p = 0.036). This report documents the presence of viruses in the lower airways of patients with acute HP. The findings may imply a potential role for influenza A in the modulation of HP during antigen exposure.

Acute Disease↗
PubMed1998

A phase I study of gemcitabine/cisplatin/etoposide in the treatment of small-cell lung cancer.

PURPOSE: To define the maximum tolerated dose and toxicity of combined cisplatin, etoposide, and gemcitabine in patients with small-cell lung cancer. METHODS: We undertook a phase I study in patients with either extensive small-cell lung cancer with or without prior chemotherapy, or limited disease who had progressed or recurred despite prior treatment. Patients received cisplatin 75 mg/m2 i.v. day 1, etoposide 50-100 mg/m2 i.v. day 1 followed by oral administration of 50-100 mg/m2 days 2 5, and gemcitabine at either 800 or 1000 mg/m2 i.v. days 1 and 8, on a 3 weekly cycle. RESULTS: We treated 20 patients, 14 at the 800 mg/m2 gemcitabine dose level, and six at the 1000 mg/m2 dose level. The protocol initially used an etoposide dose of 100 mg/m2 etoposide daily (i.v. day 1 and orally days 2-5), but the first two patients died of septic complications. With reduction of the etoposide dose to 50 mg/m2 daily x 5, the regimen was well tolerated. At this etoposide dose, neutropenia, mucositis, and gastrointestinal toxicity occurred in one patient at each of the two gemcitabine dose levels. In addition, one patient receiving gemcitabine at the 1000 mg/m2 level experienced a possible allergic reaction. The overall response rate was 54%. Patients on gemcitabine at the 800 mg/m2 level who had not received prior chemotherapy had the highest response rate, at 75%. CONCLUSION: The recommended phase II doses for this regimen are cisplatin 75 mg/m2 i.v. day 1, etoposide 50 mg/m2 i.v. day 1 and orally days 2-5, and gemcitabine 800 mg/m2 i.v. days 1 and 8. Future trials should further examine the optimal relative doses and schedule of gemcitabine and etoposide.

Adult↗
PubMed1998

Randomized study of chemotherapy and surgery versus radiotherapy for stage IIIA non-small-cell lung cancer: a National Cancer Institute of Canada Clinical Trials Group Study.

Thirty-one patients with stage IIIA (N2) non-small-cell lung cancer were randomized to receive radiotherapy alone or chemotherapy with cisplatin and vinblastine followed by surgery. Response rates to induction chemotherapy and radiotherapy were 50% and 53.3% respectively. Complete surgical resection was possible for 62.5% of patients. Median survival times were 16.2 and 18.7 months for radiotherapy alone and chemotherapy-surgery respectively (P = Ns), with no long-term improvement in survival seen with combined-modality treatment.

Adult↗
PubMed1998

Effect of route of breathing on response to exposure in a swine confinement building.

Exposure of naive subjects to swine buildings results in acute nasal, lung, and peripheral blood inflammatory responses with an increase in nonallergic airway responsiveness. Because nasal passages filter large particles and soluble gases and because swine building exposure results in an acute inflammatory response at this level, we questioned what effect breathing through or avoiding this route would have on local and systemic inflammation. Nine normal young men 23 to 37 yr of age were exposed for 5 h to a swine building, once breathing normally and once with the mouth occluded (n = 8) (Protocol 1) or the nose occluded (n = 4) (Protocol 2); three subjects participated in both protocols. For each protocol each subject underwent a methacholine challenge for PC20 measurement, a nasal lavage, venous blood puncture, and a bronchoalveolor lavage (BAL) once before and once after each swine building exposure. Bronchial responsiveness as measured by PC20 decreased in most subjects after swine building exposure and was not influenced by the route of breathing. Nasal lavage neutrophils increased tenfold after each swine exposure, except when the nose was occluded where no alteration was observed. Total BAL cells significantly increased after each exposure to the swine building, this increase was not modified by the route of breathing. In Protocol 1, white blood cells increased from a baseline level of 7.0 to 10.5 x 10(9) cells/L after exposure with normal breathing and to 10.7 x 10(9) cells/L during nasal breathing exclusively. For Protocol 2, these respective values were: 5.6, 11.7 and 10.4 x 10(9)/L. Interleukins 6 and 8 levels in BAL, nasal washes, and serum were increased by swine building exposure, except in the nasal wash when the nose was occluded. In conclusion, the lung and blood responses to exposure in a swine confinement building are not modified by the route of breathing, suggesting that nasal inflammation and filtration are not important in the process and that small respirable particles and/or gases may be responsible for these responses.

Adult↗
PubMed1998

Hypersensitivity pneumonitis in peat moss processing plant workers.

A nonsmoking 54-yr-old man, employed in a peat moss packaging plant, developed dyspnea and recurrent fever. The diagnosis of hypersensitivity pneumonitis (HP) was made. Thirteen of 14 coworkers and 13 nonexposed control subjects were studied. Five workers were nonsmokers, two were minimal smokers, and six were smokers. HP was found in another subject. Monocillium sp. and Penicillium citreonigrum, 4.6 x 10(7) CFU/g, were found in the peat moss. Three nonsmokers, the two minimal smokers (including the subject with HP), and the index case had antibodies to these microorganisms; none of the six heavy smokers had antibodies. Serum TNF-alpha was higher in the workers than in the control subjects (0.930 +/- 0.177 versus 0. 350 +/- 0.076). Three of the four asymptomatic seropositive workers and two seronegative smokers were further evaluated. All three seropositive workers had normal lung functions and CT but they all had a lymphocytic alveolitis (30, 34, and 68% lymphocytes in their bronchoalveolar lavage [BAL]). The smokers had normal lung functions, CT, and percentage of BAL lymphocytes (3 and 13%). This study identified a previously unrecognized work environment that can lead to HP and documented a protective effect of smoking on the response to antigens.

Agricultural Workers' Diseases↗
PubMed1998

Role of interleukin-2 in the development and persistence of lymphocytic alveolitis in farmer's lung.

Farmer's lung (FL) is characterized by an intense lymphocytic alveolitis which persists after an acute episode with continuous exposure to the offending antigens. This study aimed to examine the role of interleukin-2 (IL-2) in the development and persistence of this lymphocytic alveolitis. Three groups of dairy farmers were studied: acute FL, ex-FL (past history of FL but no clinical evidence of active disease) and asymptomatic farmers (no lung disease). IL-2 was measured by enzyme immunosorbent assay and T-cell proliferation was evaluated by 3H-thymidine incorporation. Acute and ex-FL patients had more lymphocytes (p<0.01) and higher levels of IL-2 (p<0.05) in their bronchoalveolar lavage (BAL) than asymptomatic farmers. BAL T-lymphocytes from acute and ex-FL patients released considerable amounts of IL-2 after stimulation with concanavalin A and showed dose-dependent proliferative responses to IL-2. IL-2 production was decreased after treatment with prednisone. Acute FL patients, but not ex-FL, had higher levels of soluble CD25 in their serum than asymptomatics (p=0.009). These results suggest that interleukin-2 may play a role in farmer's lung by providing a stimulus not only for the accumulation of lymphocytes but also for their persistence at the site of hypersensitivity reaction, and that the lung is a likely source of this cytokine in vivo.

Acute Disease↗
PubMed1997

Surfactant modifies the lymphoproliferative activity of macrophages in hypersensitivity pneumonitis.

Alveolar macrophages (AM) from normal individuals suppress mitogen-induced peripheral blood mononuclear cell (PBMC) proliferation, whereas cells from patients with hypersensitivity pneumonitis (HP) enhance PBMC. Because surfactant components can interfere with AM functions, we tested the effect of Survanta (a modified bovine surfactant) and surfactant fractions isolated from bronchoalveolar lavage of normal subjects and HP patients on AM-induced lymphoproliferation. Surfactant fractions were isolated from bronchoalveolar lavage fluids by differential centrifugation into total aggregates (TA) and large aggregates (LA). Surfactant preparations (200 micrograms/ml) from 10 normal subjects (N) or 12 HP patients or of Survanta were added to AM-PBMC cocultures stimulated with phytohemagglutinin (PHA) at 1:1 and 2:1 ratios. Results, expressed as percent of PHA-induced PBMC proliferation cocultures without surfactant, show that normal surfactant and Survanta decrease mitogen-induced proliferation of cells to a larger extent than surfactant from HP patients. For AM-to-PBMC ratios of 1:1, the results were as follows: N TA 10.58 +/- 2.75% (mean +/- SE), N LA 12.96 +/- 2.78%, HP TA 43.09 +/- 7.81%, HP LA 61.64 +/- 7.77%, and Survanta 16.70 +/- 2.95%. Similar data were obtained in 2:1 cocultures. Because surfactant components interact with AM, alterations of surfactant composition in lymphocytic diseases, mainly in the LA fraction, may account for the lack of suppressive activity in AM of HP patients and the observed alveolitis.

Adult↗
PubMed1997

Positive human health effects of dust suppression with canola oil in swine barns.

A crossover trial was conducted to evaluate the acute human health effects of a dust control technology in a swine confinement facility. Twenty lifetime nonsmoking male subjects, with no evidence of allergy or asthma and no previous swine barn exposure, participated in the study, which included a laboratory session (baseline), 5-h exposure in a swine room sprinkled with canola oil (treatment) and 5-h exposure in a traditional swine room (control). Mean values of inhalable dust concentrations and endotoxin levels in the control room were significantly greater than those observed in the treatment room. Mean shift changes in FEV1 from preexposure to end of exposure were 1.1% (standard error, 0.63%) on baseline day, -1.9% (0.63%) on treatment day, and -9.9% (1.12%) on control day; the differences in the shift changes were statistically significant. Mean value of methacholine concentration that reduced the FEV1 by 20% (PC20) in bronchoprovocation tests on baseline day was significantly different from that on treatment day (p = 0.04) and that on control day (p < 0.001). Significant increases were also observed in white blood cell counts and nasal lavage cell counts on the control day in comparison with the other two days. Blood neutrophil counts after control room exposure were twice those observed on baseline and after exposure to the treatment room. Significant differences were also observed in IL-1 beta, IL-6, and IL-8 nasal lavage cytokines and in IL-6 serum cytokine. These results suggest that the canola oil dust control method is effective in improving indoor air quality in swine barns and reducing acute health effects in naive healthy subjects.

Adolescent↗
PubMed1997

Effects of repeated swine building exposures on normal naive subjects.

Exposure to swine confinement buildings has a negative impact on respiratory health. A short exposure to this environment results in an acute airway inflammatory response. The present study was performed to confirm and further define the acute effects of working in a swine building, and to determine whether these effects are reproducible. Seven previously nonexposed normal subjects underwent evaluations that included hourly measurement of forced expiratory volume in one second (FEV1), methacholine challenge (the provocative concentration producing a 20% fall in FEV1 (PC20)), bronchoalveolar lavage (BAL), nasal lavage (NL), and blood analyses, before (control) and after each of two 5 h exposures to a swine building environment. The exposures were conducted 8 days apart. The levels of total dust, endotoxins, and ammonia (NH3) in the confinement building were measured on each day of exposure. Both exposures resulted in a significant reduction in FEV1 (mean+/-SEM change in FEV1: control = 7+/-2%; exposure 1 = 15+/-3%; exposure 2 = 23+/-3%), decrease in PC20 (median value (25th-75th percentile): 223 (23-256), 20 (15-198) and 20 (11-71), respectively; p=0.05) and increase in BAL cells (129+/-20, 451+/-43 and 511+/-103x10(3) cells x mL(-1), respectively) and NL cells (6+/-4, 126+/-58 and 103+/-26x10(3) cells x mL(-1), respectively), mostly neutrophils. Levels of interleukin-8 (IL-8), but not interleukin-1 (IL-1) or tumour necrosis factors (TNF-alpha), increased both in BAL and nasal fluids with exposure. In normal naive subjects, repeated exposure to the environment of a swine building induced a marked and reproducible reduction in forced expiratory volume in one second, increase in airway responsiveness, and increased neutrophilic inflammatory response. These results could not be accounted for by any of the environmental factors measured.

Adult↗
PubMed1997

Diagnostic accuracy of transbronchial biopsy in acute farmer's lung disease.

STUDY OBJECTIVES: To evaluate whether transbronchial biopsy (TBB) is useful for the diagnosis of acute farmer's lung (FL) by calculating the likelihood ratios (LHRs) of (1) simple pathologic criteria and (2) an overall assessment of the biopsy specimens. DESIGN: Retrospective study in which a blinded analysis of 105 TBBs with adequate material from patients with parenchymal diseases (55 cases of FL matched with 50 control samples) was performed by two independent pathologists. SETTING: Respiratory clinic of a university-affiliated referral center. MEASUREMENTS: Three pathologic criteria were first studied: (1) diffuse lymphocytic infiltration (LI); (2) focal LI; and (3) granulomas. Then, an overall assessment or the TBB was done. Four diagnostic categories were considered: (1) probable FL; (2) possible FL; (3) nonspecific; and (4) alternative diagnosis. LHRs favoring the diagnosis of FL were calculated for the pathologic criteria and for each diagnostic category. RESULTS: For both the pathologic criteria and the overall assessments, the interobserver agreement was fair. As a pathologic criterion, "diffuse LI" was better than "loosely formed granuloma" to discriminate FL from control samples (LHR, 9.1 [confidence interval, 2.2 to 37.0] vs 1.8 [confidence interval, 0.5 to 6.9]). After the overall assessment, as many as 48.6% of the TBBs were read as nonspecific. The LHRs of the four diagnostic categories were as follows: (1) probable FL: 1.1 (observer 1) and 2.6 (observer 2); (2) possible FL: 2.2 and 1.7; (3) nonspecific: 0.9 and 0.6; and (4) alternative diagnosis: 0.4 and 0.0. CONCLUSION: Hematoxylin-eosin-stained TBB specimen is of limited usefulness for the diagnosis of FL and should be reserved for patients with intermediate pretest probability of FL. Diffuse LI best discriminates FL from control samples and should be specifically sought.

Acute Disease↗
PubMed1997

Phase II trial of gemcitabine and weekly cisplatin for advanced non-small cell lung cancer.

Single-agent gemcitabine, when given in doses of > or = 1,250 mg/m2 weekly x 3 with a 1-week break, induces responses in approximately 20% of untreated patients with non-small cell lung cancer. This phase II study was undertaken to determine the efficacy of weekly administration of gemcitabine 1,500 mg/m2 combined with cisplatin 30 mg/m2 x 3 with a rest period of 1 week. Patients younger than 75 years were eligible if they had stage III/IV non-small cell lung cancer, a life expectancy > or = 12 weeks, hemoglobin > or = 10 g/dL, absolute granulocyte count > or = 10(9)/L, platelets > or = 100 x 10(9)/L, hepatic enzymes no more than three times the upper limit of normal, and serum creatinine < or = 130 micromol/L. There were 22 men and 18 women, with a median age of 60 years; 35 had a performance status of 0 or 1. Pathology included adenocarcinoma in 22 patients, squamous cell carcinoma in nine, large cell carcinoma in seven, and mixed non-small cell lung cancer in two. Six patients had stage III and 34 had stage IV tumors. Of the 39 patients eligible for response evaluation, partial remission was seen in 10, for an overall response rate of 26% (95% confidence interval, 12% to 41%). The median duration of response was 19 weeks (range, 7 to 32+ weeks). Grade 3/4 anemia was seen in 11 patients, and 21 patients required red blood cell transfusions. Grade 3/4 neutropenia occurred in 22 patients and grade 3/4 thrombocytopenia in 21 patients. One patient experienced febrile neutropenia Hematologic toxicity, particularly thrombocytopenia, was cumulative over time. Nonhematologic toxicity was modest, but one patient stopped therapy because of a grade 2 skin rash and one stopped because of a grade 4 pulmonary toxicity, both of which were thought to be related to gemcitabine. The modest activity of weekly gemcitabine and weekly cisplatin seen in this trial does not suggest in vivo synergy for these two agents as administered using this schedule and these doses.

Adult↗
PubMed1996

Viral infection enhances the response to Saccharopolyspora rectivirgula in mice prechallenged with this farmer's lung antigen.

Sendai viral infection enhances mice lung response to Saccharopolyspora rectivirgula (SR). The mechanisms of this viral enhancement remain unclear. The present study was done to verify if the viral infection was required and if the presence of the viral infection needed to be given simultaneously with the SR antigen for the enhanced response to occur. In a first experiment groups of C57BL/6 mice were instilled concomitantly with SR and live or inactivated Sendai virus. In a second experiment the viral infection in the appropriate group preceded the SR challenges by 4 weeks. As reported previously SR induced a cellular inflammatory response. This effect of SR was enhanced by the viral infection but not by inactivated virus particles. Total lavage cells 3 weeks after the virus inoculation in the appropriate groups were: saline = 69 +/- 15 x 10(3); SR = 678 +/- 104 x 10(3); Sendai = 277 +/- 61 x 10(3); inactivated Sendai = 73 +/- 23 x 10(3); SR + Sendai = 1232 +/- 232 x 10(3); SR + inactivated Sendai = 515 +/- 54 x 10(3). In the second experiment, where the infection preceded the SR challenge, no enhancement was observed. We conclude that Sendai virus enhances mice lung response to SR by an infectious process when both SR and the virus are present simultaneously.

Animals↗
PubMed1996

Phase II study of docetaxel (taxotere) in patients with previously untreated extensive small cell lung cancer.

The objective of this multicenter phase II study was to evaluate the activity of docetaxel in previously untreated small cell lung cancer. Fourteen patients were treated at a dose of 75 mg/m2 intravenously every three weeks. Of the 12 patients evaluable for response, one had a partial response for a duration of 12 weeks for a response rate of 8.3%. Toxicity was mild. We conclude that docetaxel has, at the dose given in this study, little activity in previously untreated small cell lung cancer.

Aged↗
PubMed1996

Phase I trial of gemcitabine and cisplatin in advanced non-small cell lung cancer: a preliminary report.

A phase I trial was performed to investigate the tolerability and efficacy of the novel nucleoside analogue gemcitabine in combination with cisplatin in the treatment of advanced non-small cell lung cancer. Both cisplatin and gemcitabine were administered as 30 min infusions weekly x 3 with a week of rest. There was one dose escalation of cisplatin from 25 mg/m2 (dose level 1) to 30 mg/m2 (in subsequent dose levels 2-5), such that the mean dose intensity for the weekly x 3 q 4 week cycle was 22.5 mg/m2/week which is close to that achieved with 100 mg/m2 bolus monthly. Gemcitabine was initiated at 1000 mg/m2 (dose levels 1 and 2) then escalated by 250 mg/m2/week to 1750 mg/m2 (dose level 5). Of 32 chemotherapy-naive patients entered (22 males, 10 females; median age 61 years, range 29-74 years), 11 had localized tumours (2 stage IIIa, 9 IIIb) and 21 had stage IV tumours with haematogenous metastases and a poor prognosis. Twenty-one patients had adenocarcinoma, 4 squamous cell carcinoma, 6 large cell undifferentiated tumors, and one had mixed squamous and adenocarcinoma. Dose-limiting toxicity was not seen in more than one patient in cycle 1 at any dose level. Grade 4 granulocytopenia and thrombocytopenia occurred more frequently with repeated dosing, necessitating dose reductions except at the lowest dose level (cisplatin 25 mg/m2, gemcitabine 1000 mg/m2). Non-haematological toxicity was mild and rapidly reversible. Cisplatin administration led to a higher frequency of nausea and vomiting than that seen with gemcitabine alone, but this was easily controlled with antiemetics. In the 28 patients evaluable, to date responses have been seen at most dose levels, with an overall response rate 35.7%. This phase I trial is ongoing and further dose escalation is intended to determine the MTD of gemcitabine.

Adult↗
PubMed1996

Tallimustine is inactive in patients with previously treated small cell lung cancer. A phase II trial of the National Cancer Institute of Canada Clinical Trials Group.

Tallimustine binds to the minor groove of DNA where it alkylates the N3 position of adenine and may interfere with gene transcription. We conducted a phase II trial of Tallimustine given at a dose of 750 micrograms/m2 intravenously every 4 weeks in patients with small cell lung cancer progressing or relapsing following cisplatin or carboplatin-based chemotherapy. We treated 14 eligible patients with a performance status 0, 1 or 2, bi-dimensionally measurable disease and adequate end-organ function. The main toxicity was neutropenia with a median granulocyte count of 0.1 x 10(9) per liter (range 0-3.9) and four patients (27%) developing febrile neutropenia. In addition, most patients (93%) experienced lethargy. No objective responses were seen. A mixed response was seen in one patient and three others had stable disease for a median of 3.7 months. We conclude that Tallimustine is an ineffective agent in previously treated small cell lung cancer.

Aged↗
PubMed1996

Effect of contact avoidance or treatment with oral prednisolone on bronchoalveolar lavage surfactant protein A levels in subjects with farmer's lung.

BACKGROUND: Surfactant protein A (SP-A) acts as an immune system modulator in the lungs and may therefore be involved in the pathogenesis of hypersensitivity pneumonitis. METHODS: The levels of SP-A in bronchoalveolar lavage (BAL) fluid were measured in 20 subjects with acute farmer's lung, 16 asymptomatic dairy farmers, and 14 normal controls. Eight patients had a second evaluation after one month of treatment by either contact avoidance (n = 3) or oral prednisolone (20 or 25 mg/day, n = 5). Chest radiographs and lung function measurements were also obtained in all farmers, twice in those re-evaluated after treatment. RESULTS: Patients with acute farmer's lung had significantly higher levels of SP-A than asymptomatic farmers and normal controls (p = 0.005) with mean (SE) values of 1.43 (0.29) micrograms/ml, 0.62 (0.09) microgram/ml, and 0.68 (0.11) microgram/ml, respectively. In eight subjects tested after one month of treatment the level of SP-A was unchanged although all were clinically improved. No correlations were seen between levels of SP-A in BAL fluid and numbers of BAL cells, lung function measurements, or chest radiographic scores. CONCLUSION: Although the level of SP-A is increased in the BAL fluid of patients with acute farmer's lung, it is not correlated with clinical abnormalities of this disease.

Adult↗